No circadian rhythms in testis: Period1 expression is clock independent and developmentally regulated in the mouse

Mol Endocrinol. 2003 Jan;17(1):141-51. doi: 10.1210/me.2002-0184.

Abstract

Spermatogenesis is a process whereby haploid spermatozoa differentiate through meiosis from precursor stem cells. We examined the expression of circadian clock genes in the testis, to assess clock control over the timing of different developmental events. Clock genes are known to oscillate with circadian rhythmicity in the central clock structure, the suprachiasmatic nucleus of the hypothalamus, but also in peripheral tissues. Here we show that Per1 gene expression in the testis is constant over a 24-h period and that the Per1 transcript is expressed at a level higher than the peak values of the Per1 oscillations observed for other tissues. Bmal1, another clock gene whose expression oscillates in other tissues, also shows constant expression levels in the testis. In addition, the levels and phosphorylation state of the PER1 protein are not oscillating at all times of day. Strikingly, Per1 is restricted primarily to step 7 to 10 spermatids and thus appears to be developmentally regulated. The expression of the Clock transcript is also developmentally regulated, but it is found principally in spermatogonia and spermatocytes up until the time of the first meiotic division. Per1 expression is not altered in testes from Clock mutant mice, suggesting that CLOCK does not activate Per1 in male germ cells, in contrast to what it does in other mouse tissues. Taken together, our observations suggest that the testis, in contrast to all other peripheral tissues, lacks a functioning circadian clock.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • CLOCK Proteins
  • Cell Cycle Proteins
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Gene Expression Regulation, Developmental*
  • LIM Domain Proteins
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins
  • RNA / metabolism
  • Spermatocytes / metabolism
  • Spermatogenesis / genetics*
  • Spermatogonia / metabolism
  • Testis / metabolism*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • Fhl5 protein, mouse
  • LIM Domain Proteins
  • Nuclear Proteins
  • Per1 protein, mouse
  • Period Circadian Proteins
  • Trans-Activators
  • Transcription Factors
  • activator of CREM in testis (ACT)
  • RNA
  • CLOCK Proteins
  • Clock protein, mouse